Preterm Prelabor Rupture of Membranes and Outcome of Very-Low-Birth-Weight Infants in the German Neonatal Network

Objective

It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation.

Design

Observational, epidemiological study design.

Setting

Population-based cohort, German Neonatal Network (GNN).

Population

6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth).

Methods

Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age.

Results

PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes.

Conclusions

The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM.     

Influence of lighting environment on social preferences in sticklebacks from two different photic habitats.I.mate preferences of wild-caught females

Ultraviolet (UV) A signals (320–400 nm) are important in mate choice in numerous species. The sensitivity for UV signals is not only assumed to be costly, but also expected to be a function of the prevailing ecological conditions. Generally, those signals are favored by selection that efficiently reach the receiver. A decisive factor for color signaling is the lighting environment, especially in aquatic habitats, as the visibility of signals, and thus costs and benefits, are instantaneously influenced by it. Although ecological aspects of color signal evolution are relatively well-studied, there is little data on specific effects of environmental UV-light conditions on signaling at these shorter wavelengths. We studied wild-caught gravid female 3-spined sticklebacks Gasterosteus aculeatus of 2 photic habitat types (tea-stained and clear-water lakes), possessing great variation in their UV transmission. In 2 treatments, tea-stained and clear-water, preferences for males viewed under UV-present (UV+) and UV-absent (UV–) conditions were tested. A preference for males under UV+ conditions was found for females from both habitat types, thus stressing the significance of UV signals in stickleback’s mate choice decisions. However, females from both habitat types showed the most pronounced preferences for males under UV+ conditions under clear-water test conditions. Moreover, reflectance measurements revealed that the carotenoid-based orange-red breeding coloration in wild-caught males of both habitat types differed significantly in color intensity (higher in clear-water males) and hue (more red shifted in clear-water males) while no significant differences in UV coloration were found. The differential reflection patterns in longer wavelengths suggest that sticklebacks of both habitat types have adapted to the respective water conditions. Adaptations of UV signals in a sexual context to ambient light conditions in both behavior and coloration seem less evident.     

Acetyl Coenzyme A Synthetase (ADP Forming) from the Hyperthermophilic Archaeon Pyrococcus furiosus: Identification, Cloning, Separate Expression of the Encoding Genes, acdAI and acdBI, in Escherichia coli, and In Vitro Reconstitution of the Active Heterotetrameric Enzyme from Its Recombinant Subunits

Acetyl-coenzyme A (acetyl-CoA) synthetase (ADP forming) represents a novel enzyme in archaea of acetate formation and energy conservation (acetyl-CoA + ADP + P(i) --> acetate + ATP + CoA). Two isoforms of the enzyme have been purified from the hyperthermophile Pyrococcus furiosus. Isoform I is a heterotetramer (alpha(2)beta(2)) with an apparent molecular mass of 145 kDa, composed of two subunits, alpha and beta, with apparent molecular masses of 47 and 25 kDa, respectively. By using N-terminal amino acid sequences of both subunits, the encoding genes, designated acdAI and acdBI, were identified in the genome of P. furiosus. The genes were separately overexpressed in Escherichia coli, and the recombinant subunits were reconstituted in vitro to the active heterotetrameric enzyme. The purified recombinant enzyme showed molecular and catalytical properties very similar to those shown by acetyl-CoA synthetase (ADP forming) purified from P. furiosus.     

Sexual Antagonism,Temporally Fluctuating Selection,and Variable Dominance Affect a Regulatory Polymorphism in Drosophila melanogaster

Understanding how genetic variation is maintained within species is a major goal of evolutionary genetics that can shed light on the preservation of biodiversity. Here, we examined the maintenance of a regulatory single-nucleotide polymorphism (SNP) of the X-linked Drosophila melanogaster gene fezzik. The derived variant at this site is at intermediate frequency in many worldwide populations but absent in populations from the ancestral species range in sub-Saharan Africa. We collected and genotyped wild-caught individuals from a single European population biannually over a period of 5 years, which revealed an overall difference in allele frequency between the sexes and a consistent change in allele frequency across seasons in females but not in males. Modeling based on the observed allele and genotype frequencies suggested that both sexually antagonistic and temporally fluctuating selection may help maintain variation at this site. The derived variant is predicted to be female-beneficial and mostly recessive; however, there was uncertainty surrounding our dominance estimates and long-term modeling projections suggest that it is more likely to be dominant. By examining gene expression phenotypes, we found that phenotypic dominance was variable and dependent upon developmental stage and genetic background, suggesting that dominance may be variable at this locus. We further determined that fezzik expression and genotype are associated with starvation resistance in a sex-dependent manner, suggesting a potential phenotypic target of selection. By characterizing the mechanisms of selection acting on this SNP, our results improve our understanding of how selection maintains genetic and phenotypic variation in natural populations.     

The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target

The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir’s potency. A model compound, sofalcone, both inhibits the exonuclease activity of SARS-CoV-2, SARS-CoV, and MERS-CoV in vitro, and synergistically enhances the antiviral effect of remdesivir, suppressing the replication of SARS-CoV-2 and the related human coronavirus OC43. The validation of top hits from our primary screenings using cellular systems provides proof-of-concept for the NSP14 complex as a therapeutic target.Subject terms: DNA repair enzymes, Microbiology, Infectious diseases     

Clients'' interpretation of risks provided in genetic counseling.

Clients in 544 genetic counseling sessions who were given numeric risks of having a child with a birth defect between 0% and 50% were asked to interpret these numeric risks on a five-point scale, ranging from very low to very high. Whereas clients' modal interpretation varied directly with numeric risks between 0% and 15%, the modal category of client risk interpretation remained "moderate" at risks between 15% and 50%. Uncertainty about normalcy of the next child increased as numeric risk increased, and few clients were willing to indicate that the child would probably or definitely be affected regardless of the numeric risk. Characteristics associated with clients' "pessimistic" interpretations of risk, identified by stepwise linear regression, included increased numeric risk, discussion in depth during the counseling session of whether they would have a child, have a living affected child, discussion of the effects of an affected child on relationships with client's other children, and seriousness of the disorder in question (causes intellectual impairment). Client interpretations are discussed in terms of recent developments in cognitive theory, including heuristics that influence judgments about risks, and implications for genetic counseling.     

Studies on the mechanisms involved in iron transfer across the isolated guinea pig placenta by means of bolus experiments

Placental binding and uptake of diferric transferrin as well as transplacental iron transfer has been studied in isolated, perfused guinea pig placenta. The process of binding and uptake of transferrin was saturable only on the maternal side. On the fetal side no specific binding occurred. This indicates an asymmetric distribution of transferrin receptors. No receptors are present for albumin, neither on maternal, nor fetal side. Most of the 125I-59Fe transferrin, administered with a single bolus, enters the trophoblast. A small part remains attached to the plasma membranes, as shown by cell fractionation and in transferrin exchange experiments. The majority transferrin, which was internalized, is unlikely to be bound to plasma membranes and may be bound to receptors dissociated from plasma membranes. Based on kinetics of 59Fe appearance and washout at the fetal side of the perfused placenta as a model for trans-placental iron transfer has been postulated. A central feature is the role played by a small compartment (0.14 mumol) to which iron is supplied by a very rapid process at the trophoblast receptor, without internalisation of transferrin. A second un-identified pathway is supposed to regulate the magnitude of the iron transfer pool.     

Deletion at chromosome 16p13.3 as a cause of Rubinstein-Taybi syndrome: clinical aspects.

In the accompanying paper, a chromosomal localization of the Rubinstein-Taybi syndrome by cytogenetic investigations with fluorescence in situ hybridization techniques at chromosome 16p13.3 is described. We investigated 19 of these patients and their parents (a) to ascertain the parental origin of the chromosome with the deletion in families where such a deletion was detected, (b) to disclose whether uniparental disomy plays a role in etiology, and (c) to compare clinical features in patients with a deletion to those in individuals in whom deletions were not detectable. Molecular studies showed a copy of chromosome 16 from each parent in all 19 patients. Uniparental disomy was also excluded for five other chromosome arms known to be imprinted in mice. None of the probes used for determining the origin of the deleted chromosome proved to be informative. The clinical features were essentially the same in patients with and without visible deletion, with a possible exception for the incidence of microcephaly, angulation of thumbs and halluces, and partial duplication of the halluces. A small deletion at 16p13.3 may be found in some patients with Rubinstein-Taybi syndrome. Cytogenetically undetectable deletions, point mutations, mosaicism, heterogeneity, or phenocopy by a nongenetic cause are the most probable explanations for the absence of cytogenetic or molecular abnormalities in other patients with Rubinstein-Taybi syndrome.